Evidence map›Paper›PMID 31515132›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles.

Mariane Melo, Ely Porter, Yuan Zhang, Murillo Silva, Na Li, Brian Dobosh, Alessia Liguori, Pat Skog, Elise Landais, Sergey Menis and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Controlling timing and location in vaccines.Advanced drug delivery reviews · 2020
    Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Research progress of mosquito-borne virus mRNA vaccines.Molecular therapy. Methods & clinical development · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 1 country.

Mariane MeloKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Ely PorterSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yuan ZhangKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Murillo SilvaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.
Na LiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.
Brian DoboshSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alessia LiguoriCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
Pat SkogCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
Elise LandaisCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
Sergey MenisCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
Devin SokCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
David NemazeeCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA.
William R SchiefCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; International AIDS Vaccine Initiative, The Scripps Research Institute, La Jolla, CA, USA; Immunology and Microbial Science, TSRI, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Ron WeissKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA.
Darrell J IrvineKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; Materials Science & Engineering, MIT, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: djirvine@mit.edu.
Scripps Research Institute · USMassachusetts Institute of Technology · USInternational AIDS Vaccine Initiative · USHoward Hughes Medical Institute · USIIT@MIT · USRagon Institute of MGH, MIT and Harvard · US

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Kristin A Knouse · 1985 to 2026
$93.9M
Virology and ImmunologyP01AI048240 · NIAID · UNIVERSITY OF WASHINGTON · PI RUPRECHT, RUTH MARGRIT · 2000 to 2020
$46.7M
Vaccine Adjuvant/ Delivery Systems CoreP01AI104715 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ALLEN, TODD M · 2013 to 2017
$12.3M
Knock-in mice expressing germline-reverted broadly neutralizing HIV antibodiesR01AI073148 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2007 to 2023
$8.2M
Designing and optimizing candidate HIV vaccines and boosting protocolsR01AI128836 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2017 to 2021
$4.8M
Immune Tolerance in Non-Clonal Immune SystemsR37AI059714 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2014 to 2020
$3.5M
Synthetic biology-regulated RNA vaccinesR01EB025854 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IRVINE, DARRELL J, WEISS, RON · 2018 to 2021
$2.8M
NCI NIH HHS P30 CA014051NIAID NIH HHS P01 AI048240NIAID NIH HHS P01 AI104715NIAID NIH HHS R01 AI073148NIAID NIH HHS R01 AI128836NIAID NIH HHS R37 AI059714NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462NIBIB NIH HHS R01 EB025854
6 · The paper itself

Abstract

RNA replicons are a promising platform technology for vaccines. To evaluate the potential of lipid nanoparticle-formulated replicons for delivery of HIV immunogens, we designed and tested an alphavirus replicon expressing a self-assembling protein nanoparticle immunogen, the glycoprotein 120 (gp120) germline-targeting engineered outer domain (eOD-GT8) 60-mer. The eOD-GT8 immunogen is a germline-targeting antigen designed to prime human B cells capable of evolving toward VRC01-class broadly neutralizing antibodies. Replicon RNA was encapsulated with high efficiency in 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based lipid nanoparticles, which provided effective delivery in the muscle and expression of luciferase lasting ∼30 days in normal mice, contrasting with very brief and low levels of expression obtained by delivery of equivalent modified mRNA (modRNA). eOD-GT8 60-mer-encoding replicons elicited high titers of gp120-specific antibodies following a single injection in mice, and increased levels of antigen-specific germinal center B cells compared with protein immunization. Immunization of transgenic mice expressing human inferred-germline VRC01 heavy chain B cell receptors that are the targets of the eOD antigen led to priming of B cells and somatic hypermutation consistent with VRC01-class antibody development. Altogether, these data suggest replicon delivery of Env immunogens may be a promising avenue for HIV vaccine development.

Indexed as

AIDS VaccinesAnimalsAntibodies, NeutralizingB-LymphocytesEncephalitis Virus, Venezuelan Equineenv Gene Products, Human Immunodeficiency VirusFemaleGene Knock-In TechniquesHIV-1HIV AntibodiesHIV AntigensHIV InfectionsHumansImmunizationMaleMiceAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesHIV Antigens

Identifiers

PMID31515132
PMCPMC6904793
OpenAlexW2969694946

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.